scholarly journals A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis

2017 ◽  
Vol 32 (1) ◽  
pp. 130-142 ◽  
Author(s):  
Bianca Williams ◽  
Jason Correnti ◽  
Amanke Oranu ◽  
Annie Lin ◽  
Victoria Scott ◽  
...  
2017 ◽  
Author(s):  
Maximilian Bielohuby ◽  
Surya Prakash ◽  
Bodo Brunner ◽  
Anja Pfenninger ◽  
Ulrich Werner ◽  
...  

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wen Chen ◽  
Chenzhou Wu ◽  
Yafei Chen ◽  
Yuhao Guo ◽  
Ling Qiu ◽  
...  

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.


2021 ◽  
Vol 22 (5) ◽  
pp. 2435
Author(s):  
Marzia Beccaccioli ◽  
Manuel Salustri ◽  
Valeria Scala ◽  
Matteo Ludovici ◽  
Andrea Cacciotti ◽  
...  

Fusarium verticillioides causes multiple diseases of Zea mays (maize) including ear and seedling rots, contaminates seeds and seed products worldwide with toxic chemicals called fumonisins. The role of fumonisins in disease is unclear because, although they are not required for ear rot, they are required for seedling diseases. Disease symptoms may be due to the ability of fumonisins to inhibit ceramide synthase activity, the expected cause of lipids (fatty acids, oxylipins, and sphingolipids) alteration in infected plants. In this study, we explored the impact of fumonisins on fatty acid, oxylipin, and sphingolipid levels in planta and how these changes affect F. verticillioides growth in maize. The identity and levels of principal fatty acids, oxylipins, and over 50 sphingolipids were evaluated by chromatography followed by mass spectrometry in maize infected with an F. verticillioides fumonisin-producing wild-type strain and a fumonisin-deficient mutant, after different periods of growth. Plant hormones associated with defense responses, i.e., salicylic and jasmonic acid, were also evaluated. We suggest that fumonisins produced by F. verticillioides alter maize lipid metabolism, which help switch fungal growth from a relatively harmless endophyte to a destructive necrotroph.


2021 ◽  
Vol 22 (5) ◽  
pp. 2713
Author(s):  
Sun-Hye Shin ◽  
Kyung-Ah Cho ◽  
Hee-Soo Yoon ◽  
So-Yeon Kim ◽  
Hee-Yeon Kim ◽  
...  

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.


2006 ◽  
Vol 41 (7) ◽  
pp. 820-825 ◽  
Author(s):  
Eric A. G. Demoncheaux ◽  
David A. Elphick ◽  
Marc B. Dürner ◽  
Gail E. Higgins ◽  
David Crowther ◽  
...  

2017 ◽  
Vol 21 (12) ◽  
pp. 3565-3578 ◽  
Author(s):  
Ye-Ryung Kim ◽  
Giora Volpert ◽  
Kyong-Oh Shin ◽  
So-Yeon Kim ◽  
Sun-Hye Shin ◽  
...  

2006 ◽  
Vol 398 (3) ◽  
pp. 531-538 ◽  
Author(s):  
Yukiko Mizutani ◽  
Akio Kihara ◽  
Yasuyuki Igarashi

The LASS (longevity assurance homologue) family members are highly conserved from yeasts to mammals. Five mouse and human LASS family members, namely LASS1, LASS2, LASS4, LASS5 and LASS6, have been identified and characterized. In the present study we cloned two transcriptional variants of hitherto-uncharacterized mouse LASS3 cDNA, which encode a 384-amino-acid protein (LASS3) and a 419-amino-acid protein (LASS3-long). In vivo, [3H]dihydrosphingosine labelling and electrospray-ionization MS revealed that overproduction of either LASS3 isoform results in increases in several ceramide species, with some preference toward those having middle- to long-chain-fatty acyl-CoAs. A similar substrate preference was observed in an in vitro (dihydro)ceramide synthase assay. These results indicate that LASS3 possesses (dihydro)ceramide synthesis activity with relatively broad substrate specificity. We also found that, except for a weak display in skin, LASS3 mRNA expression is limited almost solely to testis, implying that LASS3 plays an important role in this gland.


2001 ◽  
Vol 276 (32) ◽  
pp. 30261-30269 ◽  
Author(s):  
Timothy R. Henion ◽  
Dapeng Zhou ◽  
David P. Wolfer ◽  
Firoze B. Jungalwala ◽  
Thierry Hennet

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Qian Zhang ◽  
Jin-yan Wang ◽  
Wei Yan ◽  
Dan-dan Wang ◽  
Su-jin Yang ◽  
...  

Abstract Homo sapiens ceramide synthase 2 (CerS-2) plays an important role in inhibiting invasion and metastasis of tumor cells and has been reported as a tumor metastasis suppressor gene in diverse cancers. Thus, low level of CerS-2 protein might suggest a bad prognosis and up-regulation of CerS-2 protein might act as a promising therapeutic strategy for malignant tumors. In this review, we discussed the expression, as well as the clinical and pathological significance of CerS-2 in diverse human cancers. The pathological processes and molecular pathways regulated by CerS-2 were also summarized.


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